It is known that glutamic acid which is one of natural amino acids has toxicity to neurocyte (Akaike Akinori, Folia Pharmacol. Jpn. 103, 193-201 (1994), etc.). A substance inhibiting glutamic acid toxicity to neurocyte is employable as a brain metabolism activating agent or a brain metabolism improving agent.
Seto et al. reported that sugar moiety-containing dihydrophenazinecarboxylic acid derivatives represented by the below-mentioned formulas (A) and (B) [aestivophoenins A & B] which were isolated from actinomyces belonging to genus Streptomyces inhibit glutamic acid toxicity and shows antioxidant property: J. Antibiotics, 48, 1378 (1995) and PCT WO96/22996. ##STR2##
Further, a dihydrophenazinecarboxylic acid derivative having no sugar moiety which is represented by the following formula (C): ##STR3## is known {Ann. Chim. [13], 1, 115(1956)].
Also known is a compound of the following formula (D) which has no sugar moiety (benthophoenin): ##STR4## and its methyl ester. These compounds are reported to be employable as a free radical scavenger (anti-oxidant). [J. Nat. Prod., 56, 1255(1993)].
Also known is a compound of the following formula (E) which has no sugar moiety: ##STR5## wherein R represents hydrogen, methyl or nitro [Helv. Chim. Acta, 52, 322(1969)].
Also known is a compound of the following formula (F) which has no sugar moiety: ##STR6## [J. Gen. Microbiol., 104, 299(1978)].
As for the above-mentioned dihydrophenazinecarboxylic acid derivatives having no sugar moiety, the publications give no description concerning inhibition of glutamic acid toxicity.
The compound having the aforementioned formula (D) is obtained only from the mycelium of Streptomyces prunicolor.
The compounds having the aforementioned formulas (A) and (B) which are reported to show inhibition of glutamic acid toxicity are natural products. It is not expected to produce enough amounts of these compounds by culture. Further, it is difficult to prepare these compounds by organic synthetic methods because the compounds have L-rhamnose residue in the molecular structure. Until now, no reports have been given on total synthesis of these compounds or their analogs.
Accordingly, it is desired to provide dihydrophenazinecarboxylic acid derivatives which show inhibition of glutamic acid toxicity and which are easily synthesized.